Effects of l-theanine on anxiety-like behavior, cerebrospinal fluid amino acid profile, and hippocampal activity in Wistar Kyoto rats

Abstract

Rationale and objectives

The amino acid l-theanine (N-ethyl-l-glutamine) has historically been considered a relaxing agent. In the present study, we examined the effects of repeated l-theanine administration on behavior, levels of amino acids in the cerebrospinal fluid (CSF), and hippocampal activity in Wistar Kyoto (WKY) rats, an animal model of anxiety and depressive disorders.

Methods

Behavioral tests were performed after 7–10 days of l-theanine (0.4 mg kg−1 day−1) or saline administration, followed by CSF sampling for high-performance liquid chromatography (HPLC) analysis. An independent set of animals was subjected to [18F]fluorodeoxyglucose positron emission tomography (PET) scanning after the same dose of l-theanine or saline administration for 7 days.

Results

In the elevated plus maze test, the time spent in the open arms was significantly longer in the l-theanine group than in the saline group (P = 0.035). In addition, significantly lower CSF glutamate (P = 0.039) and higher methionine (P = 0.024) concentrations were observed in the l-theanine group than in the saline group. A significant increase in the standard uptake value ratio was observed in the hippocampus/cerebellum of the l-theanine group (P < 0.001).

Conclusions

These results suggest that l-theanine enhances hippocampal activity and exerts anxiolytic effects, which may be mediated by changes in glutamate and methionine levels in the brain. Further study is required to more fully elucidate the mechanisms underlying the effects of l-theanine.

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Acknowledgements

The authors would like to thank Mr. Makoto Funasaka for his expert technical assistance with the PET experiments and Ms. Midori Ninomiya for her instructions on rat CSF collection.

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Correspondence to Hiroshi Kunugi.

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This research study was funded by an unrestricted research grant provided by Taiyo Life Insurance Himawari Foundation, Tokyo, Japan. This funding agency had no role in the design, methods, analysis, or preparation of the paper.

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Ogawa, S., Ota, M., Ogura, J. et al. Effects of l-theanine on anxiety-like behavior, cerebrospinal fluid amino acid profile, and hippocampal activity in Wistar Kyoto rats. Psychopharmacology 235, 37–45 (2018). https://doi.org/10.1007/s00213-017-4743-1

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Keywords

  • Amino acids
  • Cerebrospinal fluid
  • [18F]Fluorodeoxyglucose
  • l-Theanine (N-ethyl-L-glutamine)
  • Positron emission tomography
  • Wistar Kyoto rats